PARIS and TARRYTOWN, N.Y.—While the investigational agent aflibercept (VEGF Trap) for the second-line treatment of non-small cell lung cancer (NSCLC) in development by sanofi-aventis and Regeron Pharmaceuticals Inc. didn't meet the primary endpoint in its Phase III VITAL trial, it did meet secondary targets. The companies will conduct a detailed analysis of the efficacy and safety results of the VITAL study, and full results will be presented at an upcoming medical meeting.

According to sanofi and Regeneron, the data showed that adding aflibercept to the chemotherapy drug docetaxel did not meet the pre-specified criteria for the primary endpoint of improvement in overall survival compared with a regimen of docetaxel plus placebo. But the addition of aflibercept to docetaxel demonstrated activity as measured by key secondary endpoints of the study: progression free survival and an overall objective response rate of 23.3 percent in the aflibercept arm compared to 8.9 percent in the placebo arm.

The treatment emergent adverse events on the aflibercept arm, with an incidence that was 10 percent greater than the control arm, were stomatitis, weight decrease, hypertension, epistaxis and dysphonia. Grade 3 or 4 adverse events that occurred at a frequency of at least 5 percent in patients who received aflibercept were fatigue, stomatitis, disease progression, hypertension, febrile neutropenia, dyspnea, neutropenia and asthenia. Events leading to treatment discontinuation occurred in 27.2 percent of patients in the aflibercept arm compared to 14.6 percent in the placebo arm. The types and frequencies of adverse events reported in the aflibercept treatment arm were generally consistent with those reported in previous studies with anti-VEGF agents, the companies report.

"Bringing new and innovative cancer therapies to patients can be incredibly challenging, especially in difficult-to-treat cancers such as second-line non-small cell lung cancer," notes Debasish Roychowdhury, senior vice president and head of sanofi-aventis' Global Oncology Division. "Our Phase III trials of aflibercept in metastatic colorectal cancer and hormone-refractory metastatic prostate cancer are underway to determine the clinical potential of aflibercept for patients with these advanced cancers."

The VITAL study was a multinational, randomized, double-blind trial comparing aflibercept versus placebo in combination with docetaxel patients with locally advanced or metastatic non-squamous NSCLC who have failed one platinum-based therapy. The study enrolled 913 patients who were randomized to receive intravenous (IV) docetaxel 75 mg/m2 plus either IV placebo or IV aflibercept 6 mg/kg every three weeks until disease progression, unacceptable toxicity, patient's refusal or further treatment. The primary objective of the study was to demonstrate improvement in overall survival with the combination of aflibercept and docetaxel compared with placebo and docetaxel.

Regeneron and sanofi are collaborating on a broad oncology development program, combining the investigational agent aflibercept with common chemotherapy regimens in the treatment of patients with advanced cancers. In addition to VITAL, the program includes two Phase III trials and one Phase II trial, all of which are fully enrolled:

VELOUR: Second-line treatment for metastatic colorectal cancer in combination with 5-fluorouracil, leucovorin and irinotecan (FOLFIRI) (Phase III). Final results are anticipated during the first half of 2011.

VENICE: First-line treatment for hormone-refractory metastatic prostate cancer in combination with docetaxel and prednisone (Phase III). An interim analysis is expected to be conducted by an Independent Data Monitoring Committee in mid 2011; final results are anticipated in 2012.

AFFIRM: First-line treatment in metastatic colorectal cancer in combination with 5-fluorouracil, leucovorin and oxaliplatin (FOLFOX) (Phase II). Final results are expected during the second half of 2011.

Aflibercept is an investigational angiogenesis inhibitor with a unique mechanism of action, say sanofi and Regeneron. This fusion protein binds all forms of Vascular Endothelial Growth Factor-A (VEGF-A), as well as VEGF-B and placental growth factor (PIGF), which are additional angiogenic growth factors that appear to play a role in tumor angiogenesis and inflammation. Aflibercept has been shown to bind VEGF-A, VEGF-B and PlGF with higher affinity than their natural receptors.